MadSci Network: Neuroscience

Re: MAO inhibition and DMT

Date: Wed Feb 3 21:38:37 1999
Posted By: Gabriel Vargas, Post-doc/Fellow, Neurosciences/Psychiatry, UCSF
Area of science: Neuroscience
ID: 916816047.Ns

N,N-dimethyltryptamine (DMT), is an hallucinogenic tryptamine analog, and 
an endogenous mammalian hallucinogen.
Extensive behavioral and biochemical evidence suggests an agonist role at 
the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of 
action of hallucinogenic drugs.  DMT behaves as an agonist at both 5-HT2A 
and 5-HT2C receptors.  One difference is in that the 5-HT2C, but not the 
5-HT2A, receptor shows a profound desensitization to DMT over time. This 
difference is interesting in light of the recent report that the 
hallucinogenic activity of DMT  does not tolerate in humans and suggests 
the 5-HT2C receptor plays a less prominent role in the action of DMT.
DMT is not orally active but can be made so by use of MAO Inhibitors.
	Hallucinogenic effects seen with DMT include a rapidly moving, 
brightly colored visual display of images. Auditory effects were less 
common. "Loss of control," associated with a brief, but overwhelming 
"rush," led to a dissociated state, where euphoria alternated or coexisted 
with anxiety. These effects completely replaced subjects' previously 
ongoing mental experience and were more vivid and compelling than dreams or 
waking awareness.  Thus in answer to your question, yes DMT is endogenous 
and can be made more available through the use of MAOI.  Whether this 
explains near-death experiences I am not sure.  It seems that you would 
expect a more psychedelic experience than the images most people report 
which are more consistent with an opioid type of response, a feeling of 
calm and tranquility.


Smith, RL; Canton, H; Barrett, RJ; Sanders-Bush, E.  Agonist properties of
N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors.
Pharmacology, Biochemistry and Behavior, 1998 Nov, 61(3):323-30. 

Strassman, RJ; Qualls, CR; Berg, LM.  Differential tolerance to biological 
an subjective effects of four closely spaced doses ofN,N-dimethyltryptamine 
in humans.
Biological Psychiatry, 1996 May 1, 39(9):784-95. 

Hope this helps,

gabriel vargas md/phd


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